SH2-domain containing inositol phosphatase (SHIP) is a 145 kDa multi-domain cytosolic protein expressed specifically in hematopoietic cells that negatively regulates cell growth, survival and proliferation. SHIP hydrolyzes the phospholipid product phosphoinositol 3,4,5-trisphosphate of PI3K. Specifically, SHIP converts PI(3,4,5)P3 to PI(3,4)P2. This serves to regulate cell survival, proliferation, and differentiation. In this manner, SHIP influences the survival and/or function of numerous cell types, including myeloid cells, osteoclasts, and NK cells.
In genetic models of germline and induced SH2-domain containing inositol 5-phosphatase (SHIP) deficiency, SHIP deficient hosts are permissive for engraftment of major histocompatibility complex (MHC) mismatched bone marrow (BM) grafts, exhibit reduced graft-versus-host disease (GVHD) post-transplant and have delayed rejection of vascularized MHC mismatched heart grafts (unpublished data). In addition, SHIP-deficient mice show an expansion and mobilization of hematopoietic stem cells (HSC) to the blood and spleen. Moreover, recent findings have shown that phosphoinositol phosphatases are important regulators of signaling pathways relevant to both diabetes and cancer.